Novel protein, process for producing the same and use therof

Abstract

The present invention relates to a novel SSD(sterol-sensing domain)-containing protein derived from human liver, human testis and human brain, or a salt thereof, and a DNA encoding the same. Studies on the tissue-specificity of the protein expression, the expression change depending the intracellular cholesterol level, production of the transformant, and the site-specific expression in brain regions of a patient with Alzheimer's disease are disclosed.

1 . A protein or salt thereof, comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 16.  
     
     
         2 . The protein or salt thereof according to  claim 1 , comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 17.  
     
     
         3 . The protein or salt thereof according to  claim 1 , comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 34.  
     
     
         4 . The protein or salt thereof according to  claim 1 , comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 35.  
     
     
         5 . The protein or salt thereof according to  claim 1 , comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 40.  
     
     
         6 . A protein or salt thereof, comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, but not comprising the amino acid sequence shown by SEQ ID NO. 38.  
     
     
         7 . The protein or salt thereof according to  claim 6 , comprising the same or substantially the same amino acid sequence as the 22-th to 1332-th residues of the amino acid sequence shown by SEQ ID NO: 9.  
     
     
         8 . DNA comprising DNA containing a nucleic acid sequence encoding (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, but not comprising the amino acid sequence shown by SEQ ID NO. 38.  
     
     
         9 . The DNA of  claim 8 , comprising (i) the nucleic acid sequence of 64-th to 3999-th bases of the nucleic acid sequence shown by SEQ ID NO: 7, (ii) the nucleic acid sequence shown by SEQ ID NO: 15, (iii) the nucleic acid sequence shown by SEQ ID NO: 32, (iv) the nucleic acid sequence shown by SEQ ID NO: 33, or (v) the nucleic acid sequence shown by SEQ ID NO: 41.  
     
     
         10 . A recombinant vector comprising DNA of  claim 8 .  
     
     
         11 . A transformant transformed with the recombinant vector of  claim 10 .  
     
     
         12 . A method of producing (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, but not comprising the amino acid sequence shown by SEQ ID NO. 38, or salt thereof, comprising culturing the transformant of  claim 11  to produce the protein.  
     
     
         13 . An antibody to (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, but not comprising the amino acid sequence shown by SEQ ID NO. 38, or salt thereof.  
     
     
         14 . A medicine comprising (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof.  
     
     
         15 . A medicine comprising DNA of  claim 8 .  
     
     
         16 . The medicine of  claim 14  or  15  which is a prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy.  
     
     
         17 . A diagnostic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising DNA of  claim 8  or antibody of  claim 13 .  
     
     
         18 . A method of screening a compound or salt thereof promoting or inhibiting the activity of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, characterized by use of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof.  
     
     
         19 . A kit for screening a compound or salt thereof promoting or inhibiting the activity of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, the kit comprising (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof.  
     
     
         20 . A compound or salt thereof promoting or inhibiting the activity of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 18  or the screening kit of  claim 19 .  
     
     
         21 . A medicine comprising a compound or salt thereof promoting or inhibiting the activity of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 18  or the screening kit of  claim 19 .  
     
     
         22 . A prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising a compound or salt thereof promoting the activity of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 18  or the screening kit of  claim 19 .  
     
     
         23 . A method of screening a compound or salt thereof changing the sterol-sensing ability of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, characterized by use of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof.  
     
     
         24 . A kit for screening a compound or salt thereof changing the sterol-sensing ability of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, the kit comprising (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof.  
     
     
         25 . A compound or salt thereof changing the sterol-sensing ability of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 23  or the screening kit of  claim 24 .  
     
     
         26 . A medicine comprising a compound or salt thereof changing the sterol-sensing ability of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 23  or the screening kit of  claim 24 .  
     
     
         27 . A prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising a compound or salt thereof enhancing the sterol-sensing ability of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 23  or the screening kit of  claim 24 .  
     
     
         28 . A method of quantifying mRNA of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, characterized by use of DNA of  claim 8  or a part thereof.  
     
     
         29 . A method of quantifying (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, characterized by use of the antibody of  claim 13 .  
     
     
         30 . A method of diagnosing diseases related to the functions of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, characterized by use of the quantifying method of  claim 28  or  29 .  
     
     
         31 . A method of screening a compound or salt thereof changing the expression amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, characterized by use of the quantifying method of  claim 28 .  
     
     
         32 . A compound or salt thereof changing the expression amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, obtainable using the screening method of  claim 31 .  
     
     
         33 . A medicine comprising a compound or salt thereof changing the expression amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, obtainable using the screening method of  claim 31 .  
     
     
         34 . A prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising a compound or salt thereof increasing the expression amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, obtainable using the screening method of  claim 31 .  
     
     
         35 . A method of screening a compound or salt thereof changing the intracellular amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, characterized by use of the quantifying method of  claim 29 .  
     
     
         36 . A compound or salt thereof changing the intracellular amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, obtainable using the screening method of  claim 35 .  
     
     
         37 . A medicine comprising a compound or salt thereof changing the intracellular amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, obtainable using the screening method of  claim 35 .  
     
     
         38 . A prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising a compound or salt thereof increasing the intracellular amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, obtainable using the screening method of  claim 35 .  
     
     
         39 . A prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising a compound or salt thereof having an action on an SSD-containing protein to manifest the regulation of intracellular cholesterol transport.  
     
     
         40 . A method of preventing and treating diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising administering to a mammal an effective amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof.  
     
     
         41 . A method of preventing and treating diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising administering to a mammal an effective amount of DNA of  claim 8 .  
     
     
         42 . A method of preventing and treating diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising administering to a mammal an effective amount of a compound or salt thereof promoting the activity of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 18  or the screening kit of  claim 19 .  
     
     
         43 . A method of preventing and treating diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising administering to a mammal an effective amount of a compound or salt thereof enhancing the sterol-sensing ability of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 23  or the screening kit of  claim 24 .  
     
     
         44 . A method of preventing and treating diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising administering to a mammal an effective amount of a compound or salt thereof increasing the expression amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, obtainable using the screening method of  claim 31 .  
     
     
         45 . A method of preventing and treating diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy, comprising administering to a mammal an effective amount of a compound or salt thereof having an action on an SSD-containing protein to manifest the regulation of intracellular cholesterol transport.  
     
     
         46 . Use of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, for producing a prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy.  
     
     
         47 . Use of DNA of  claim 8 , for producing a prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy.  
     
     
         48 . Use of a compound or salt thereof promoting the activity of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 18  or the screening kit of  claim 19 , for producing a prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy.  
     
     
         49 . Use of a compound or salt thereof enhancing the sterol-sensing ability of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, or salt thereof, obtainable using the screening method of  claim 23  or the screening kit of  claim 24 , for producing a prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy.  
     
     
         50 . Use of a compound or salt thereof increasing the expression amount of (i) the protein of  claim 1  or (ii) a protein comprising the same or substantially the same amino acid sequence as that shown by SEQ ID NO: 8, obtainable using the screening method of  claim 31 , for producing a prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy.  
     
     
         51 . Use of a compound or salt thereof having an action on an SSD-containing protein to manifest the regulation of intracellular cholesterol transport, for producing a prophylactic and/or therapeutic agent for diabetes mellitus, obesity, cancer, arterial sclerosis, hyperlipidemia, neurodegenerative diseases or neuropathy.